Personalising treatment for myeloma patients based on initial response to NHS treatment and their overall fitness level

Immunotherapy approaches adapted for fitness in newly diagnosed transplant ineligible patients with Myeloma

Status

Recruiting

Phases

Phase 3

Study type

Interventional

Source

ISRCTN

Registry ID

ISRCTN98606172

Enrollment

1226

Registered

2026-06-01

Start date

2026-06-26

Completion date

Unknown

Last updated

2026-08-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Multiple myeloma

Interventions

All participants receive six cycles of standard of care induction treatment with DRd. Each treatment cycle is 28 days. At the end of the six cycles, participants will undergo an MRD response assessme

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: Inclusion criteria for registration: 1. Newly diagnosed as having symptomatic MM, plasma cell leukaemia or non-secretory MM according to IMWG diagnostic criteria 2014, 2. Considered not suitable to receive autologous stem cell transplant as part of their first line therapy by the treating clinician, 3. Planned for treatment with Daratumumab, Lenalidomide and dexamethasone (DRd) as first line therapy as standard of care, 4. Aged 18 years or greater, 5. Able to provide full informed consent, and 6. Prepared to comply with pregnancy prevention plan. Inclusion criteria for randomisation into all iFIT1/iFIT2/iFIT3 pathways: • Completed 6 cycles of DRd induction therapy after registering within the iFIT study, • Able to provide full informed consent, and • Prepared to comply with pregnancy prevention plan. Inclusion criteria specific to randomisation pathways: • Dexamethasone may have been stopped due to toxicity and the participant will remain eligible (iFIT1 and iFIT3), • Planned to continue on at least daratumumab (monthly) and lenalidomide (at any dose level) (iFIT1 and iFIT3), • Planned to continue on all three DRd medications (dose reductions are allowed) (iFIT2), • Achieved a partial response (PR) biochemically (irrespective of MRD status) or achieved a =VGPR and are MRD positive, as confirmed by HMDS (central laboratory) (iFIT1 and iFIT2), • Achieved a =VGPR and are MRD negative, as confirmed by HMDS (central laboratory) (iFIT3), • Categorised as FIT or UNFIT according to the IMWG frailty index (iFIT1), • Categorised as FRAIL according to the IMWG frailty index (iFIT2), and • Meet the blood criteria specified in the protocol within 14 days before randomisation (haematological and biochemical) (iFIT1). Full inclusion criteria are listed in the protocol.

Exclusion criteria

Exclusion criteria: Exclusion criteria for registration: 1. Smouldering myeloma (SMM), primary amyloidosis, solitary plasmacytoma of bone or extramedullary plasmacytoma (without additional evidence of myeloma), 2. Pregnant, breastfeeding, plans to become pregnant, or plans to father a child whilst enrolled in the study or within 3 months after the last dose, 3. Previous treatment for myeloma, except as specified in the protocol, 4. Active systemic viral, fungal or bacterial infection requiring systemic therapy. Criteria for specific chronic infections clarified in the protocol, or 5. Participation in any other interventional study for myeloma that involves an IMP during treatment and active monitoring. Exclusion criteria for randomisation into all iFIT1/iFIT2/iFIT3 pathways: • Received systemic anti-myeloma therapy other than DRd prior to randomisation. Steroids given (by any route) for reasons other than myeloma disease control are allowed, • Received a stem cell transplant, • Participation in any other interventional study for myeloma that involves an IMP during treatment and active monitoring, and • Pregnant, breast feeding, plans to become pregnant, or plans to father a child whilst enrolled in the study or within a specified period after the last dose. Exclusion criteria specific to randomisation pathways: • Stable disease (SD) or progressive disease (PD) as per IMWG response criteria (iFIT1 and iFIT2), • Partial response (PR), stable disease (SD) or progressive disease (PD) as per IMWG response criteria (iFIT3), and • Further exclusion criteria related to safety of interventions (iFIT1). Full exclusion criteria are listed in the protocol.

Design outcomes

Primary

Measure	Time frame
Measured using eCRFs and patient records, unless otherwise indicated. If disease response is required, this is measured in accordance with the IMWG Uniform Response Criteria for Multiple Myeloma. iFIT1: Progression-free survival, measured as the time from iFIT1 randomisation to progression or death from any cause. Participants alive and progression-free at the time of analysis will be censored at their last known date to be alive and progression-free. iFIT2: Event-free survival, measured as the time from iFIT2 randomisation to the first of the following events: grade 4 haematological adverse events (AEs) (anaemia, neutropenia, thrombocytopenia), grade 3 and 4 non-haematological AEs (including secondary primary malignancies; SPMs), discontinuation of trial treatment, progression or death. Events will be graded according to NCI-CTCAE V5. Participants event-free at the time of analysis will be censored at their last date known to be alive and event-free. iFIT3: iFIT3 has co-primary endpoints. Progression-free survival, measured as the time from iFIT3 randomisation to progression or death from any cause. Participants alive and progression-free at the time of analysis will be censored at their last known date to be alive and progression-free. Participant-reported overall health and quality of life, measured using the EORTC QLQ-C30 global health status (GHS)/QoL scale score at 30 months after iFIT3 randomisation.	—

Measure

Time frame

Measured using eCRFs and patient records, unless otherwise indicated. If disease response is required, this is measured in accordance with the IMWG Uniform Response Criteria for Multiple Myeloma. iFIT1: Progression-free survival, measured as the time from iFIT1 randomisation to progression or death from any cause. Participants alive and progression-free at the time of analysis will be censored at their last known date to be alive and progression-free. iFIT2: Event-free survival, measured as the time from iFIT2 randomisation to the first of the following events: grade 4 haematological adverse events (AEs) (anaemia, neutropenia, thrombocytopenia), grade 3 and 4 non-haematological AEs (including secondary primary malignancies; SPMs), discontinuation of trial treatment, progression or death. Events will be graded according to NCI-CTCAE V5. Participants event-free at the time of analysis will be censored at their last date known to be alive and event-free. iFIT3: iFIT3 has co-primary endpoints. Progression-free survival, measured as the time from iFIT3 randomisation to progression or death from any cause. Participants alive and progression-free at the time of analysis will be censored at their last known date to be alive and progression-free. Participant-reported overall health and quality of life, measured using the EORTC QLQ-C30 global health status (GHS)/QoL scale score at 30 months after iFIT3 randomisation.

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Secondary

Measure	Time frame
Measured using eCRFs and patient records, unless otherwise indicated. If disease response is required, this is measured in accordance with the IMWG Uniform Response Criteria for Multiple Myeloma. 1. Progression-free survival (iFIT2 only), measured from iFIT2 randomisation to progression or death from any cause. Participants alive and progression-free at the time of analysis will be censored at their last known date to be alive and progression-free. 2. Time to progression, measured from iFIT1/iFIT2/iFIT3 randomisation to first documented evidence of disease progression. Participants who died without progression will be censored at their date of death. Participants alive and progression-free at the time of analysis will be censored at their last known date to be alive and progression-free. 3. Time to second PFS event, measured from iFIT1/iFIT2/iFIT3 randomisation to the second documented evidence of PD or death from any cause. Participants alive and for whom a second progression has not been observed at the time of analysis will be censored at their last known date to be alive and second progression-free. 4. Overall survival, measured from iFIT1/iFIT2/iFIT3 randomisation to death from any cause. Participants alive at the time of analysis will be censored at their last known date to be alive. 5. Event-free survival (iFIT1 only), measured from iFIT1 randomisation to the first of the following events: grade 4 haematological AEs (anaemia, neutropenia, thrombocytopenia), grade 3 and 4 non-haematological AEs (including SPMs), discontinuation of trial treatment, progression, or death. Participants event-free at the time of analysis will be censored at their last date known to be alive and event-free. 6. Survival after progression, measured from first documented evidence of disease progression to death from any cause. Participants alive at the time of analysis will be censored at their last known date to be alive. This endpoint is only defined for those who experience progre	—

Measure

Time frame

Measured using eCRFs and patient records, unless otherwise indicated. If disease response is required, this is measured in accordance with the IMWG Uniform Response Criteria for Multiple Myeloma. 1. Progression-free survival (iFIT2 only), measured from iFIT2 randomisation to progression or death from any cause. Participants alive and progression-free at the time of analysis will be censored at their last known date to be alive and progression-free. 2. Time to progression, measured from iFIT1/iFIT2/iFIT3 randomisation to first documented evidence of disease progression. Participants who died without progression will be censored at their date of death. Participants alive and progression-free at the time of analysis will be censored at their last known date to be alive and progression-free. 3. Time to second PFS event, measured from iFIT1/iFIT2/iFIT3 randomisation to the second documented evidence of PD or death from any cause. Participants alive and for whom a second progression has not been observed at the time of analysis will be censored at their last known date to be alive and second progression-free. 4. Overall survival, measured from iFIT1/iFIT2/iFIT3 randomisation to death from any cause. Participants alive at the time of analysis will be censored at their last known date to be alive. 5. Event-free survival (iFIT1 only), measured from iFIT1 randomisation to the first of the following events: grade 4 haematological AEs (anaemia, neutropenia, thrombocytopenia), grade 3 and 4 non-haematological AEs (including SPMs), discontinuation of trial treatment, progression, or death. Participants event-free at the time of analysis will be censored at their last date known to be alive and event-free. 6. Survival after progression, measured from first documented evidence of disease progression to death from any cause. Participants alive at the time of analysis will be censored at their last known date to be alive. This endpoint is only defined for those who experience progre

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Countries

England, United Kingdom

Contacts

Public ContactEmma McNaught

ctru-ifit@leeds.ac.uk+44 113 3431978

Outcome results

None listed

Source: ISRCTN (via WHO ICTRP) · Data processed: Aug 10, 2026